Cushing syndrome (CS) during pregnancy is a rare condition with only a few cases reported in the literature. Misdiagnosis of CS is common because of overlapping features like
fatigue,
weight gain, striae and emotional changes that can occur during normal pregnancy. Changes in maternal
hormones and their
binding proteins complicate assessment of
glucocorticoid hormone levels during gestation. CS during pregnancy is most frequently due to an adrenal
adenoma and to a lesser degree to
adrenocorticotropic hormone (
ACTH) hypersecretion by a
pituitary adenoma. Furthermore, aberrant expression of
luteinizing hormone (
LH) receptors in the adrenal cortex has been suggested to be involved in the pathogenesis of adrenal CS during pregnancy. We report three pregnant women with
ACTH-independent
Cushing's syndrome and an adrenal
tumor. After uncomplicated delivery, patient 1 underwent in vivo testing for aberrant
hormone receptor expression by the
adenoma.
Cortisol responses were found after administration of
luteinizing hormone-releasing hormone (
LHRH),
human chorionic gonadotropin (hCG),
glucagon,
vasopressin and a standard mixed meal. All patients were treated with laparoscopic
adrenalectomy. Adrenal
tumor tissue of two patients showed positive immunohistochemical staining of
LH receptors. Considering the
cortisol responses to
LHRH and hCG, and the development of CS during pregnancy in these patients, it is likely that
ACTH-independent
hypercortisolism was induced by the pregnancy-associated rise in hCG levels that activated aberrantly expressed
LH receptors in the adrenal
adenoma. Remarkably, adrenal
adenomas may simultaneously express multiple aberrant receptors and individual
ligands may play a role in the regulation of
cortisol production in CS during pregnancy.